Controlled vagal blockage therapy

ABSTRACT

A method for treating at least one of a plurality of disorders characterized at least in part by vagal activity includes positioning an electrode around a body organ innervated by the vagus. An electrical signal is applied to the electrode to modulate vagal activity. The electrical signal is applied at a frequency selected for the signal to create a neural conduction block to the vagus with the neural conduction block selected to at least partially block nerve impulses on the vagus. The application of the electrical signal is discontinued. The application of the signal and the discontinuing of the signal are repeated with durations of the discontinuing and the application selected to treat the disorder.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/276,638, filed Oct. 19, 2011, now U.S. Pat. No. 8,538,533; which is acontinuation of U.S. patent application Ser. No. 12/908,375, filed Oct.20 2010, now U.S. Pat. No. 8,046,085; which is a continuation of U.S.patent application Ser. No. 10/881,045, filed Jun. 30, 2004, now U.S.Pat. No. 7,844,338; which is a continuation-in-part of U.S. patentapplication Ser. No. 10/674,324, now abandoned; Ser. No. 10/674,330, nowU.S. Pat. No. 7,489,969; and Ser. No. 10/675,818, now abandoned, allfiled Sep. 29, 2003, and U.S. patent application Ser. No. 10/752,940,now U.S. Pat. No. 7,444,183 and Ser. No. 10/752,944, now U.S. Pat. No.7,167,750, both filed Jan. 6, 2004; which patent applications are eachcontinuations-in-part of U.S. patent application Ser. No. 10/358,093,filed Feb. 3, 2003, now abandoned, which applications are incorporatedherein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains to treatments of disorders associated, at leastin part, with neural activity. These may include, without limitation,gastrointestinal, pancreo-biliary, cardio-respiratory and centralnervous system disorders (including neurological and psychiatric,psychological and panic disorders). More particularly, this inventionpertains to treatment of such disorders through management of neuralimpulse stimulation and blocking.

2. Description of the Prior Art

As disclosed in the parent applications and their related internationalpatent application Ser. Nos. PCT/US2004/002847; PCT/US2004/002841 andPCT/US2004/002849 (all incorporated herein by reference), a wide varietyof disorders can be treated by blocking neural impulses on the vagusnerves. The blocking can be used as a therapy by itself or used incombination with traditional electrical nerve stimulation. The disordersto be treated include, without limitation, functional gastrointestinaldisorders (FGIDs) (such as functional dyspepsia (dysmotility-like) andirritable bowel syndrome (IBS)), gastroparesis, gastroesophageal refluxdisease (GERD), inflammation, discomfort and other disorders. Also, theblocking therapy has described application to central nervous systemtreatments.

Treatments of gastrointestinal diseases through nerve stimulation havebeen suggested. For example, U.S. Pat. No. 6,238,423 to Bardy dated May29, 2001 describes a constipation treatment involving electricalstimulation of the muscles or related nerves of the gut. U.S. Pat. No.6,571,127 to Ben-Haim et al. dated May 27, 2003 describes increasingmotility by applying an electrical field to the GI tract. U.S. Pat. No.5,540,730 to Terry, Jr. et al., dated Jul. 30, 1996 describes a motilitytreatment involving vagal stimulation to alter GI contractions inresponse to a sense condition indicative of need for treatment. U.S.Pat. No. 6,610,713 to Tracey dated Aug. 26, 2003 describes inhibitingrelease of a proinflammatory cytokine by treating a cell with acholinergic agonist by stimulating efferent vagus nerve activity toinhibit the inflammatory cytokine cascade.

The present invention is an improvement upon a neural blocking therapyas described in the parent applications. Suggestions have been made toblock nerves in very specific ways. For example, U.S. Pat. No. 5,188,104to Wernicke et al. dated Feb. 23, 1993 describes an attempt to inhibit asubset of nerve fibers in the vagus. Specifically, the patent suggestsselectively blocking C-fibers of the vagus at a 40 Hz signal. Themaximum frequency discussed in this patent is a 150 Hz frequency. Toavoid undesired effects of vagal stimulation on organs not targeted bythe stimulation, U.S. Pat. No. 6,684,105 to Cohen et al. dated Jan. 27,2004 describes the use of collision blocks to suppress antidromiceffects of stimulation signals. Both of these blocking techniques havesignificant drawbacks. Subselection of fibers is very difficult inpractice. Collision blocking results in a signal being propagated inboth afferent and efferent directions. The parent applications teachapplication of full cross-section neural block to inhibit actionpotentials across all nerve fibers at a blocked site and therebyblocking both afferent and efferent signals.

The present invention is an improvement upon a neural blocking to avoidantidromic influences during stimulation or to otherwise down-regulatenerve activity. Cryogenic nerve blocking of the vagus is described inDapoigny et al., “Vagal influence on colonic motor activity in consciousnonhuman primates”, Am. J. Physiol., 262: G231-G236 (1992). Electricallyinduced nerve blocking is described in Van Den Honert, et al.,“Generation of Unidirectionally Propagated Action Potentials in aPeripheral Nerve by Brief Stimuli”, Science, Vol. 206, pp. 1311-1312. Anelectrical nerve block is described in Solomonow, et al., “Control ofMuscle Contractile Force through Indirect High-Frequency Stimulation”,Am. J. of Physical Medicine, Vol. 62, No. 2, pp. 71-82 (1983) andPetrofsky, et al., “Impact of Recruitment Order on Electrode Design forNeural Prosthetics of Skeletal Muscle”, Am. J. of Physical Medicine,Vol. 60, No. 5, pp. 243-253 (1981). A neural prosthesis with anelectrical nerve block is also described in U.S. Patent ApplicationPublication No. US 2002/0055779 A1 to Andrews published May 9, 2002. Acryogenic vagal block and resulting effect on gastric emptying aredescribed in Paterson C A, et al., “Determinants of Occurrence andVolume of Transpyloric Flow During Gastric Emptying of Liquids in Dogs:Importance of Vagal Input”, Dig Dis Sci, (2000); 45:1509-1516.

Constant nerve blocking (through constant blocking signal application)can be undesirable. Such a treatment can have high power requirements.Furthermore, a complete down-regulation of a nerve can be undesirablesince the nerve's desirable functions are also interrupted. It would bedesirable to more fully control the degree of down-regulation of a nerveto achieve a desired therapy while minimizing undesired effects ofcomplete or constant down-regulation.

SUMMARY OF THE INVENTION

A method is disclosed for treating at least one of a plurality ofdisorders of a patient where the disorders are characterized at least inpart by vagal activity innervating at least one of a plurality ofalimentary tract organs of the patient at an innervation site. Themethod includes positioning a neurostimulator carrier around a bodyorgan of the patient where the organ is innervated by at least a vagaltrunk or branch and with an electrode disposed on the carrier andpositioned at the vagal trunk or branch. An electrical signal is appliedto the electrode to modulate vagal activity by an amount selected totreat the disorder. The electrical signal is applied at a frequencyselected for the signal to create a neural conduction block to the trunkor branch at a blocking site with the neural conduction block selectedto at least partially block nerve impulses on the trunk at the blockingsite. The application of the electrical signal is discontinued. Theapplication of the signal and the discontinuing of the signal arerepeated with durations of the discontinuing and the applicationselected to treat the disorder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of an alimentary tract (GI tract plusnon-GI organs such as the pancreas and liver) and its relation to vagaland enteric innervation;

FIG. 2 is a schematic representation of pacing system;

FIG. 3 is the view of FIG. 1 showing the application of a nerveconduction block electrode to the alimentary tract;

FIG. 4 is a schematic representation of a patient's stomach shownpartially in section and illustrating a representative placement ofanterior and posterior vagus nerves with respect to the anatomy of thestomach and diaphragm;

FIG. 5 is the view of FIG. 4 showing placement of electrode bands;

FIG. 6 is a perspective view of a band used in FIG. 5;

FIG. 7 is a side sectional view of a patient's stomach illustrating atransesophageal electrode;

FIG. 8 is a side elevation view of a balloon portion of an apparatus foruse in the embodiment of FIG. 7;

FIG. 9 is a side elevation view of an alternative embodiment of aballoon portion of an apparatus for use in the embodiment of FIG. 7;

FIG. 10 is a side sectional view of a patient's stomach in illustratinga yet alternative embodiment of the apparatus of FIG. 7;

FIG. 11 is a side sectional view of a patient's stomach in illustratinga still further alternative apparatus of FIG. 8;

FIG. 12 is a schematic view of a balloon with magnetic coils;

FIG. 13 is a view similar to that of FIG. 3 showing the addition of asensing electrode and controller according to the present invention; and

FIG. 14 is a graphical presentation of a controlled vagal activityachieved with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENT

With reference now to the various drawing figures in which identicalelements are numbered identically throughout, a description of thepreferred embodiment of the present invention will now be described.

Description of Prior Applications

The parent applications and the afore-mentioned related internationalapplications (all incorporated herein by reference) teach variousaspects of stimulating and blocking electrodes for either up-regulatingor down-regulating the vagus nerve and combinations of these electrodesfor a wide variety of therapies. To facilitate an understanding of thepresent invention, selected portions of those applications are describedin this section.

1. Description of Vagal Innervation of the Alimentary Tract

FIG. 1 is a schematic illustration of an alimentary tract (GI tract plusnon-GI organs such as the pancreas and gall bladder, collectivelylabeled PG) and its relation to vagal and enteric innervation. The loweresophageal sphincter (LES) acts as a gate to pass food into the stomachS and, assuming adequate function of all components, prevent reflux. Thepylorus PV controls passage of chyme from the stomach S into theintestines I (collectively shown in the figures and including the largeintestine or colon and the small intestine including the duodenum,jejunum and ileum).

The biochemistry of the contents of the intestines I is influenced bythe pancreas P and gall bladder PG which discharge into the duodenum.This discharge is illustrated by dotted arrow A.

The vagus nerve VN transmits signals to the stomach S, pylorus PV,pancreas and gall bladder PG directly. Originating in the brain, thereis a common vagus nerve VN in the region of the diaphragm (not shown).In the region of the diaphragm, the vagus VN separates into anterior andposterior components with both acting to innervate the GI tract. InFIGS. 1, 3 and 13, the anterior and posterior vagus nerves are not shownseparately. Instead, the vagus nerve VN is shown schematically toinclude both anterior and posterior nerves.

The vagus nerve VN contains both afferent and efferent componentssending signals to and away from, respectively, its innervated organs.

In addition to influence from the vagus nerve VN, the GI and alimentarytracts are greatly influenced by the enteric nervous system ENS. Theenteric nervous system ENS is an interconnected network of nerves,receptors and actuators throughout the GI tract and pancreas and gallbladder PG. There are many millions of nerve endings of the entericnervous system ENS in the tissues of the GI organs. For ease ofillustration, the enteric nervous system ENS is illustrated as a lineenveloping the organs innervated by the enteric nervous system ENS.

The vagus nerve VN innervates, at least in part, the enteric nervoussystem ENS (schematically illustrated by vagal trunk VN3 whichrepresents many vagus-ENS innervation throughout the cut). Also,receptors in the intestines I connect to the enteric nervous system ENS.Arrow B in the figures illustrates the influence of duodenal contents onthe enteric nervous system ENS as a feedback to the secretion functionof the pancreas, liver and gall bladder. Specifically, receptors in theintestine I respond the biochemistry of the intestine contents (whichare chemically modulated by the pancreao-biliary output of Arrow A).This biochemistry includes pH and osmolality.

In the figures, vagal trunks VN1, VN2, VN4 and VN6 illustrateschematically the direct vagal innervation of the GI organs of the LES,stomach S, pylorus PV and intestines I. Trunk VN3 illustrates directcommunication between the vagus VN and the ENS. Trunk VN5 illustratesdirect vagal innervation of the pancreas and gall bladder. Entericnerves ENS1-ENS4 represent the multitude of enteric nerves in thestomach S, pylorus PV, pancreas and gall bladder PG and intestines I.

While communicating with the vagus nerve VN, the enteric nervous systemENS can act independently of the vagus and the central nervous system.For example, in patients with a severed vagus nerve (vagotomy—anhistorical procedure for treating ulcers), the enteric nervous systemcan operate the gut. Most enteric nerve cells are not directlyinnervated by the vagus. Gershon, “The Second Brain”, Harper CollinsPublishers, Inc, New York, N.Y. p. 19 (1998).

2. Implantable Pacing Circuit

A representative pacing circuit 100 is schematically shown in FIG. 2.Similar to cardiac pacing devices, an implantable controller 102contains an induction coil 104 for inductive electrical coupling to acoil 106 of an external controller 108. The implantable controller 102includes anterior and posterior pulse generators 110, 112 electricallyconnected through conductors 114, 116 to anterior and posterior pacingelectrodes 118, 120 for attachment to anterior and posterior trunks,respectively, of the vagus nerve VN. The implantable controller 102 alsoincludes a battery 122 and a CPU 124 which includes program storage andmemory. The timing and parameters of the pulse at the electrodes 118,120 can be adjusted by inductively coupling the external controller 108to the implantable controller 102 and inputting pacing parameters (e.g.,pulse width, frequency and amplitude).

While a fully implantable controller 102 is one possible embodiment, itis not necessary. For example, the electrodes 118, 120 can be implantedconnected to a receiving antenna placed near the body surface. Thecontrol circuits (i.e., the elements 124, 110, 112 and 108) can behoused in an external pack worn by the patient with a transmittingantenna held in place on the skin over the area of the implantedreceiving antenna. Such a design is forward-compatible in that theimplanted electrodes can be later substituted with the implantablecontroller 102 at a later surgery if desired.

Although not shown in FIG. 2, the controller 102 can also includecircuits generating nerve conduction block signals (as will bedescribed) which connect to electrodes which may be positioned on anerve proximally, distally (or both) of the electrodes 118, 120.

3. Neural Blocking Therapy

FIG. 3 illustrates a therapy application using a nerve conductionblocking electrode for providing a conduction block. A nerve block is,functionally speaking, a reversible vagotomy. Namely, application of theblock at least partially prevents nerve transmission across the site ofthe block. Removal of the block restores normal nerve activity at thesite. A block is any localized imposition of conditions that at leastpartially diminish transmission of impulses.

The block may be intermittent or continuous. The preferred nerveconduction block is an electronic block created by a signal at the vagusby an electrode PBE controlled by the implantable controller (such ascontroller 102 or an external controller). The nerve conduction blockcan be any reversible block. For example, ultrasound, cryogenics (eitherchemically or electronically induced) or drug blocks can be used. Anelectronic cryogenic block may be a Peltier solid-state device whichcools in response to a current and may be electrically controlled toregulate cooling. Drug blocks may include a pump-controlled subcutaneousdrug delivery.

With such an electrode conduction block, the block parameters (signaltype and timing) can be altered by a controller and can be coordinatedwith the pacing signals to block only during pacing. A representativeblocking signal is a 500 Hz signal with other parameters (e.g., timingand current) matched to be the same as the pacing signal. While analternating current blocking signal is described, a direct current(e.g., −70 mV DC) could be used.

The foregoing specific examples of blocking signals are representativeonly. Other examples and ranges of blocking signals are described in theafore-mentioned literature. For example, the nerve conduction block ispreferably within the parameters disclosed in Solomonow, et al.,“Control of Muscle Contractile Force through Indirect High-FrequencyStimulation”, Am. J. of Physical Medicine, Vol. 62, No. 2, pp. 71-82(1983). Particularly, the nerve conduction block is applied withelectrical signal selected to block the entire cross-section of thenerve (e.g., both afferent, efferent, myelinated and nonmyelinatedfibers) at the site of applying the blocking signal (as opposed toselected sub-groups of nerve fibers or just efferent and not afferent orvisa versa) and, more preferably, has a frequency selected to exceed the200 Hz threshold frequency described in Solomonow et al. Further,preferred parameters are a frequency of 500 Hz (with other parameters,as non-limiting examples, being amplitude of 4 mA, pulse width of 0.5msec, and duty cycle of 5 minutes on and 10 minutes off). As will bemore fully described, the present invention gives a physician greatlatitude in selected pacing and blocking parameters for individualpatients.

In certain patients, the vagus nerve activity may contribute toundesired effects such pancreatitis progression or obesity contributingfactors. Use of a blocking electrode alone in the vagus permitsdown-regulating the vagus nerve VN, the enteric nervous system ENS andpancreo-biliary output. The block down-regulates both afferent andefferent signal transmission.

In FIG. 3, the baseline vagal activity is illustrated by the solid lineof the proximal vagus nerve segment VNP. The remainder of the vagus andenteric nervous system are shown in reduced thickness to illustratedown-regulation of tone. The pancreo-biliary output (and resultingfeedback) is also reduced. In FIG. 3, the blocking electrode BE is shownhigh on the vagus relative to the GI tract innervation (e.g., just belowthe diaphragm), the sole blocking electrode could be placed lower (e.g.,just proximal to pancreo/biliary innervation VN5). Blocking of theentire vagus as described above can be used to down-regulate the vagusfor various benefits including: pancreatitis and obesity treatments.Further, blocking the vagus interrupts the vagally-mediated neurogenicinflammatory arc.

The use of blocking as an independent therapy permits treatment forpancreatitis and obesity by down regulating vagal activity andpancreatic output including pancreatic exocrine secretion. Also, theblocking may be used as a separate treatment for reducing discomfort andpain associated with gastrointestinal disorders or other vagallymediated pain (i.e., somatic pain sensations transmitted along any nervefibers with pain sensation modulated by vagal afferent fibers). A nervestimulation to treat pain is described in U.S. patent applicationpublication No. US2003/0144709 to Zabara et al., published Jul. 31,2003.

4. Application to Obesity

Obesity is treatable with vagal block. Recent literature describespotential obesity treatments relative to gut hormone fragment peptideYY₃₋₃₆. See, e.g., Batterham, et al., “Inhibition of Food Intake inObese Subjects by Peptide YY3-36”, New England J. Med., pp. 941-948(Sep. 4, 2003) and Korner et al., “To Eat or Not to Eat—How the GutTalks to the Brain”, New England J. Med., pp. 926-928 (Sep. 4, 2003).The peptide YY₃₋₃₆ (PPY) has the effect of inhibiting gut motilitythrough the phenomena of the ileal brake. Vagal afferents create asensation of satiety.

The present invention can electrically simulate the effects of PPY byusing the vagal block to down-regulate afferent vagal activity to createa desired sensation of satiety. Since the down-regulation does notrequire continuous blocking signals, the beneficial efferent signals arepermitted.

Also, vagal block restricts fundal accommodation, reduces pancreaticexocrine secretion (thereby reducing caloric absorption) andbeneficially effects both satiety and satiation.

5. Apparatus for Applying Vagal Block

a. Background

With reference to FIG. 4, a stomach S is shown schematically for thepurpose of facilitating an understanding of applying a blocking signalas illustrated in FIGS. 5-12. In FIG. 4, the stomach S is shown with acollapsed fundus F which is deflated due to fasting. In practice, thefundus F can be reduced in size and volume (as shown in FIG. 4) orexpanded (as shown in FIG. 7).

The esophagus E passes through the diaphragm D at an opening or hiatusH. In the region where the esophagus E passes through the diaphragm D,trunks of the vagal nerve (illustrated as the anterior vagus nerve AVNand posterior vagus nerve PVN) are disposed on opposite sides of theesophagus E. It will be appreciated that the precise location of theanterior and posterior vagus nerves AVN, PVN relative to one another andto the esophagus E are subject to a wide degree of variation within apatient population. However, for most patients, the anterior andposterior vagus nerves AVN, PVN are in close proximity to the esophagusE at the hiatus H where the esophagus E passes through the diaphragm D.

The anterior and posterior vagus nerves AVN, PVN divide into a pluralityof trunks that innervate the stomach directly and via the entericnervous system and may include portions of the nerves which may proceedto other organs such as the pancreas, gallbladder and intestines.Commonly, the anterior and posterior vagus nerves AVN, PVN are still inclose proximity to the esophagus E and stomach (and not yet extensivelybranched out) at the region of the junction of the esophagus E andstomach S.

In the region of the hiatus H, there is a transition from esophagealtissue to gastric tissue. This region is referred to as the Z-line(labeled “Z” in the Figures). Above the Z-line, the tissue of theesophagus is thin and fragile. Below the Z-line, the tissue of theesophagus E and stomach S are substantially thickened and more vascular.Within a patient population, the Z-line is in the general region of thelower esophageal sphincter. This location may be slightly above,slightly below or at the location of the hiatus H.

b. Implanted Band Electrode

i. Description of Device

With reference to FIG. 5, a band 200 is shown placed around theesophagus E or proximal portion of the stomach below the diaphragm D andoverlying the anterior and posterior vagus nerves AVN, PVN at thecardiac notch CN. Alternatively, it can be placed completely around theupper portion of the stomach near its junction of the esophagus.Placement of a band 200 around the esophagus E directly beneath thediaphragm D ensures that the band may be placed around the anterior andposterior vagus nerves AVN, PVN without the need for extensivedissection of the nerves AVN, PVN. In a preferred embodiment, the nervesAVN, PVN are indirectly stimulated by passing electrical signals throughthe tissue surrounding the nerves.

The band 200 may be formed of polyester or the like or any othersuitable material which may be sutured in place or otherwise fastened inplace surrounding the esophagus E or gastric cardia. Preferably, theband 200 is placed at the junction of the esophagus E and stomach S suchthat the band may overly both the esophagus E and stomach S at thecardiac notch CN.

The band 200 may have a plurality of electrodes which, in the embodimentof FIG. 5 include an upper electrode array 202 and a lower electrodearray 203. In the embodiment of FIG. 11 (in which a band 200 is shownlying flat), the electrode arrays 202, 203 are shown with electrodesplaced at an angle relative to the cylindrical axis X-X of the band 200.

Placement of the band 200 as described ensures that at least a subset ofthe electrodes 202, 203 will be in overlying relation to the anteriorand posterior vagus nerves AVN, PVN. As a result, energizing theelectrodes 202, 203 will result in stimulation of the anterior andposterior vagus nerves AVN, PVN and/or their branches.

In therapeutic applications, the upper array 202 of electrodes may beconnected to a blocking electrical signal source (with a blockingfrequency and other parameters as previously described) and the lowerarray 203 of electrodes may be connected to a stimulation electricalsignal source as previously described. Of course, only a single array ofelectrodes could be used with all electrodes connected to either ablocking or a stimulating signal.

In a preferred embodiment for treating obesity, only upper band 200 isused with both of electrodes 202, 203 being bi-polar pairs (i.e.,alternating anode and cathode electrodes) for applying a blocking signalas will be described.

The electrical connection of the electrodes 202, 203 to a controller isnot shown but may be as previously described by having a leadsconnecting the electrodes directly to an implantable controller.Alternatively, and as previously described, electrodes may be connectedto an implanted antenna for receiving a signal to energize theelectrodes.

The use of an array of electrodes permits the collar 200 to be placedwithout the need for great accuracy at the time of placement. In theevent it is desirable that electrodes not directly overlying a vagusnerve be deactivated, the electrodes could, through operation of acontroller, be individually energized to detect a physiologicalresponse. The absence of a physiological response (other than possiblemuscular action of the stomach and esophagus) would indicate the absenceof an overlying relation to a vagus nerve. The presence of aphysiological response would indicate overlying relation of the testedelectrode to a vagus nerve.

By identifying which electrodes create a physiologic response, theremaining electrodes (i.e., those not having a physiological response)could be permanently deactivated. An example of a physiological responsewould be a cardiovascular response which may be attributed to a signalof about 2-80 hertz and up to 50 milliamps and as more fully describedin U.S. Pat. No. 6,532,388 to Hill et al dated Mar. 11, 2003. As aresult, a selected one of the AVN or PVN could be energized.

It will be appreciated the foregoing description of identifyingelectrodes to be deactivated is a non-limiting embodiment. For example,all electrodes could be energized. The therapies as previously describedcould be employed by using blocking electrodes or stimulation electrodesor both in order to block or energize (or both) the vagus nerve.

FIG. 5 also illustrates an alternative embodiment in the form of a band200′ surrounding the body of the stomach S and having arrays 202′, 203′.Since the band 200′ is more distal to the esophagus E, different andmore distal trunks of the vagus nerves would be energized. Also, such aplacement would permit the option of covering the anterior vagus nervewhile not covering the posterior vagus nerve (or visa versa).

In addition to the benefits of nerve pacing, the band 200 can also beused to restrict and potentially lengthen the esophagus thereby reducingpossibilities for reflux as more fully described in commonly assignedand co-pending U.S. patent application Ser. No. 10/600,080 filed Jun.20, 2003 and entitled “Gastro-Esophageal Reflux Disease” (GERD)Treatment Method and Apparatus”.

An alternative placement of the band is to place the band at thecardia-esophagus junction or at the top of the cardia over-lying a fatpad which surrounds a patient's cardia. Such a placement is used inplacing restrictive bands such as the Lap-Band or the Swedish Band ofObtech Medical, AG. So placed, the band 200 covers both anterior andposterior vagal trunks. In most patients, this placement will result inthe band 200 not covering the hepatic branch of the vagus. However, thehepatic branch is believed to have little impact on gastric orpancreatic function.

ii. Application to Obesity and Satiety

The embodiment of FIG. 5 is particularly suitable for the treatment ofobesity. Obesity is of epidemic proportions and is associated with largedecreases in life expectancy and early mortality. Peeters, et al.,“Obesity in Adulthood and Its Consequences for Life Expectancy: A LifeTable Analysis”, Annals of Internal Medicine, Vol. 138, No. 1, pp. 24-32(2003).

In the embodiment of FIG. 5, the upper band 200 is placed around thestomach near the cardiac notch CN. Electrode array 202 may bede-activated (or not present on the band 200). Lower array 203 can beenergized with a blocking signal.

The prior art suggests stimulating the vagas with a stimulating signalfor treating obesity or eating disorders. See, e.g., U.S. Pat. No.5,188,104 to Wernicke et al., dated Feb. 23, 1993; U.S. Pat. No.5,263,480 to Wernicke et al., dated Nov. 23, 1993; U.S. Pat. No.6,587,719 to Barrett et al., dated Jul. 1, 2003 and U.S. Pat. No.6,609,025 to Barrett et al., dated Aug. 19, 2003. These patents alldescribe stimulating, non-blocking signals (e.g., stimulating to a levelslightly below a so-called “retching threshold” as described in the '025patent). As such, all fail to note the problem associated with obesityand eating discords that is not addressed by stimulating the vagus but,rather, by blocking stimulation on the vagus.

The blocking at cardiac notch CN reduces fundal accommodation andcreates satiety sensations. Such a physiologic response is suggested byvagotomy data in which truncal vagotomy patients have experienced weightloss and increased satiety. See, e.g., Kral, “Vagotomy as a Treatmentfor Morbid Obesity”, Surg. Clinics of N. Amer., Vol. 59, No. 6, pp.1131-1138 (1979), Gortz, et al., “Truncal Vagotomy Reduces Food andLiquid Intake in Man”, Physiology & Behavior, Vol. 48, pp. 779-781(1990), Smith, et al., “Truncal Vagotomy in Hypothalamic Obesity”, TheLancet, pp. 1330-1331 (1983) and Kral, “Vagotomy for Treatment of SevereObesity”, The Lancet, pp. 307-308 (1978).

The optional lower band 200′ is placed lower on the stomach (e.g., closeto the pylorus). The lower electrode array 203′ of the lower band 200′is energized with a stimulation signal to modulate intestinal motilityin the event motility is otherwise impaired by the upper band blocking.

The upper array 202′ of the lower band 200′ is energized with a blockingsignal so that the stimulation signal at electrodes 203′ does notinterfere with the blocking effect of electrodes 203 of upper band 200.In this obesity treatment, the electrodes of the bands 200, 200′ can beplaced on constricting bands (such as the well-known Lap-Band® system ofInamed Inc., Santa Barbara, Calif., USA, and used in obesity treatmentor the previously mentioned and similarly used Swedish band). Morepreferably, the bands 200, 200′ are not constricting thereby minimizingerosion risks otherwise associated with highly constricting bands.However, the neural blocking technology of the present invention can beincorporated into such constricting bands or used in conjunction otherobesity surgeries or therapies. Specifically, the scientific literatureindicates a vagotomy in combination with other obesity procedure (e.g.,antrectomy, gastroplasty and biliopancreatic bypass) improves weightloss procedures. Tzu-Ming, et al., “Long-Term Results of Duodenectomywith Highly Selective Vagotomy in the Treatment of Complicated DuodenalUlcers”, Amer. J. of Surg., Vol. 181, pp. 372-376 (2001), Kral, et al.,“Gastroplasty for Obesity: Long-Term Weight Loss Improved by Vagotomy”,World J. Surg., Vol. 17, pp. 75-79 (1993), and Biron, et al., “ClinicalExperience with Biliopancreatic Bypass and Gastrectomy or SelectiveVagotomy for Morbid Obesity”, Canadian J. of Surg., Vol. 29, No. 6, pp.408-410 (1986).

Vagal neural blocking simulates a vagotomy but, unlike a vagotomy, isreversible and controllable. Therefore, while obesity is particularlydescribed as a preferred treatment, the vagal neural block of thepresent invention can be used as a less drastic procedure for treatmentspreviously performed with a vagotomy. Without limitation, these includeobesity, ulcers or chronic pain or discomfort (alone or in combinationwith conjunctive procedures).

Further, bulimia has been identified as a disease amenable to treatmentby decreasing afferent vagal activity via pharmacological vagalinhibitors delivered systemically. Faris, et al., “Effect of DecreasingAfferent Vagal Activity with Ondansetron on Symptoms of Bulimia Nervosa:a Randomized, Double-Blind Trial”, The Lancet, pp. 792-797 (2000).Therefore, bulimia and other diseases treatable with vagal blocker drugscan be treated with the targeted and site-specific vagal neural block ofthe present invention.

c. Acute Treatment Device

i. Device Description

FIG. 7 illustrates a still further embodiment of the present inventionwhere a nasogastric tube 300 is passed into the stomach. It will beappreciated that nasogastric tubes are well known and form no part ofthis invention per se. Some nasogastric tubes have specializedfunctions. An example is a tamponade tube having gastric and esophagealballoons. An example of such is the Bard® Minnesota Four LumenEsophagogastric Tamponade Tube for the Control of Bleeding fromEsophageal Varices as described in product literature (information foruse) contained with the product of that name dated 1998 by C. R. Bard,Inc., Covington, Ga., USA. Further, while a nasogastric tube is apreferred embodiment other devices (e.g., an orogastric tube or anyelongated device to position electrodes near the esophagus/stomachjunction) could be used. Also, while placement at the esophagus/stomachjunction is preferred, the device can be placed in a different lumen(e.g., the trachea) for transmucosal stimulation.

The nasogastric tube 300 is multi-lumen tube which includes distalopenings 302 to which suction can be applied to remove gastric contentsthrough the tube 300. A compliant balloon 304 surrounds the gastrictube. Proximal to the balloon 304 is an opening 309 in communicationwith a lumen (not shown) to which a suction can be applied to removesaliva through the opening 309.

The balloon 304 has a plurality of electrodes which may include an upperarray 306 of electrodes and a lower array 307 of stimulation electrodes.The electrodes of the upper array 306 may be connected to a blockingsignal source via conductors 306 a (FIG. 13). The electrodes of thelower array 307 may be connected to a stimulation signal source viaconductors 307 a. The conductors 306 a, 307 a may be passed through alumen in the tube 300 to an external controller (not shown). As aresult, multiple electrodes can be energized for transmucosalstimulation of the anterior and posterior vagus nerves AVN, PVN. FIG. 14shows an alternative design where the arrays 306, 307 are replaced withexpandable, circumferential electrodes 306′, 307′ connected to acontroller (not shown) by conductors 306 a′, 307 a′.

As in the embodiment of FIG. 7, the individual electrodes of the arrays306, 307 may optionally be selectively energized to detect acardiovascular signal indicating an electrical coupling of theelectrodes to the vagus nerves AVN, PVN. Electrodes that do not createsuch a coupling may optionally be deactivated such that only theelectrodes having an effective coupling with the vagus nerves AVN, PVNwill be activated. Also, and as in the embodiment of FIG. 7, there maybe a single array of electrodes or all electrodes may be energized witheither a blocking or stimulation signal.

It will be noted in this embodiment that the electrodes are disposedabutting the mucosal surface of the esophageal and stomach lining andare not in direct contact with the vagus nerves AVN, PVN. Instead, theelectrodes are spaced from the vagus nerves AVN, PVN by the thickness ofthe stomach and lower esophageal wall thickness.

Transmucosal electrical stimulation of nerves is well known. Suchstimulation is disclosed in U.S. Pat. No. 6,532,388 to Hill et al datedMar. 11, 2003 (describing transmucosal stimulation of nerves across atrachea using a balloon with electrodes in the trachea to modulatecardiac activity). Also, the phenomena of transmucosal electricalstimulation of nerves is described in Accarino, et al, “SymptomaticResponses To Stimulation Of Sensory Pathways In The Jejunum”, Am. J.Physiol., Vol. 263, pp. G673-G677 (1992) (describing afferent pathwaysinducing perception selectively activated by transmucosal electricalnerve stimulation without disruption of intrinsic myoelectrical rhythm);Coffin, et al, “Somatic Stimulation Reduces Perception Of Gut DistentionIn Humans”, Gastroenterology, Vol. 107, pp. 1636-1642 (1994); Accarino,et al, “Selective Dysfunction Of Mechano Sensitive Intestinal AfferentsIn Irritable Bowel Syndrome”, Gastroenterology, Vol. 108, pp. 636-643(1994), Accarino, et al “Modification Of Small Bowel MechanosensitivityBy Intestinal Fat”, GUT, Vol. 48, pp. 690-695 (2001); Accarino, et al,“Gut Perception In Humans Is Modulated By Interacting Gut Stimuli”, Am.J. Physiol. Gastrointestinal Liver Physiol., Vol. 282, pp. G220-G225(2002) and Accarino, et al, “Attention And Distraction Colon Affects OnGut Perception”, Gastroenterology, Vol. 113, pp. 415-442 (1997).

Alternative embodiments of the transmucosal stimulation device of FIG. 7are shown in FIGS. 8 and 9. In FIG. 8, the balloon 304′ is conical inshape with a base end 304 a′ placed distally on the tube 300′. Afterexpansion, the base end 304 a′ expands within the stomach S. Thephysician then pulls on the tube 300′. The base end 304 a′ (which islarger in diameter than the esophagus E) abuts the stomach S at thecardiac notch CN acting as a stop. This insures the electrodes 305′(only a single array is shown for ease of illustration) abuts themucosal tissue at the junction of the stomach S and esophagus E. Theelectrodes 305′ are on the narrow end 304 b′ of the balloon 304′ andexpansion of the balloon 304′ ensures contact of the electrodes with themucosal tissue.

FIG. 9 illustrates an embodiment using two balloons 304″ and 309″. Thedistal balloon 309″, when expanded, is larger than the esophagus E andacts as a stop when the physician pulls on the tube 300″. The electrodes305″ are on a smaller balloon 304″ which may expand in the esophagus E.The balloon 304″, 309″ are positioned for the electrodes 305″ to beagainst the mucosal tissue at the junction of the stomach S andesophagus E when the distal balloon 309″ abuts the cardiac notch CN andthe proximal balloon 304″ is expanded. The electrodes may be positionedto be completely within the stomach to reduce risk of injury toesophageal tissue. More conveniently, a tube such as the afore-mentionedBard® tube may be modified for electrodes to be placed on the proximalside of the gastric balloon.

In all of the foregoing, a balloon is expanded to urge the electrodesagainst the mucosal tissue. While this is a presently preferredembodiment, any mechanism for urging the electrodes against the mucosaltissue may be used. In each of FIGS. 8 and 9, the tube 300′, 300″ isshown as it passes through the balloons 304′, 304″ and 309″. Thisillustration is made to indicate the tube passes through the balloonsand does terminate at the balloons. In fact, as the tube 300′, 300″passes through the balloons 304′, 304″ and 309″ it would be surroundedby the material of the balloons 304′, 304″ and 309″ and would not bevisible.

A still further embodiment is shown in FIG. 12. Instead of directlystimulating with current, the nerves are stimulated with magneticfields. In this case, the electrodes are coils 307′″ insulated withinthe balloon 304′″. The coils 307′″ create magnetic fields whichinductively couple with the vagus nerves to create the blocking andstimulating impulses within the nerves.

While FIGS. 7-12 show electrodes on a balloon, electrodes can be placedon a catheter which resides in the esophagus. For example,CardioCommand, Inc., Tampa, Fla., USA markets a product TapScope™ andother related products which include a catheter having ring electrodesspaced apart along the length of the catheter near a distal tip of thecatheter. The esophagus is a so-called “potential space” in that whenempty of contents, the catheter collapses. With a catheter in theesophagus, the esophagus collapses onto the catheter with the esophaguswall in contact with the electrodes.

The TapScope (which comes in various sizes—e.g., 5, 10 or 18 French) isused positioned high in the esophagus with the electrodes placed nearthe heart. The TapScope is stimulated to cause pacing of the heart. Suchpacing is using to perform cardiac stress testing patients. It isparticularly useful in patients who are not ambulatory or who cannottolerate more traditional stress testing (such as dobutamine stresstesting). A discussion of such use of the TapScope can be found in Lee,et al., “Nonexercise Stress Transthoracic Echocardiography:Transesophageal Atrial Pacing Versus Dobutamine Stress”, J. Amer Collegeof Cardiology, Vol. 33, No. 2 pp. 506-511 (1999).

The TapScope can be modified to lengthen the catheter to positionelectrodes near or below the diaphragm to apply a blocking signalinstead of a stimulating signal. The TapScope can also be modified toprovide a hollow center to permit concurrent use of the TapScope as agastric or jejunal tube. Further, the device can be modified to place aninflatable balloon on the catheter to reside in the stomach. Theinflated balloon acts as a stop to prevent withdrawing the catheterprematurely and insure accurate positioning of the electrodes near orbelow the diaphragm.

ii. Application to Acute Pancreatitis

When energized with a blocking frequency, the embodiment of FIG. 7 isuseful for treating acute or recurrent pancreatitis. This extremelyserious disease is characterized by an over-active pancreas whichexcretes digestive enzymes to such an extent that the pancreas itself isdigested. The disease can be extremely painful. In many cases, thedisease is fatal. The number of US patients who suffer an episode ofacute pancreatitis is approximately 185,000 annually. Baron, et al.,“Acute Necrotizing Pancreatitis”, New England J. of Medicine, Vol. 340,No. 18, pp. 1412-1417 (1999). This high incidence, coupled with the costand length of stay required, make the total cost of this disease tosociety enormous. No definitive therapy is currently available to treatthese patients except supportive care. Furthermore, the overallmortality rate for severe pancreatitis is about 20 to 30%. Id.

A recent study reported that the average total hospital cost to obtain asurvivor of severe, acute pancreatitis is nearly $130,000 with anaverage length of hospital stay of 40 days. Soran, et al., “Outcome andquality of life of patients with acute pancreatitis requiring intensivecare”, J. Surg. Res., 91(1), pp. 89-94 (2000). Further complicating themanagement of these patients is the uncertainty surrounding theprognosis because the course of the disease is unpredictable at initialpresentation. Chatzicostas, et al., “Balthazar computed tomographyseverity index is superior to Ranson criteria and APACHE II and IIscoring systems in predicting acute pancreatitis outcome”, J. ClinicalGastroenterology, 36(3), pp. 253-260 (2003). If patients could besuccessfully treated during the initial phases of the disease, with ahigher survival rate, there is a high probability of returning to aproductive life. Soran, et al., supra.

Pancreatitis may be associated with a number of etiologies includingchronic alcoholism or gallstones (e.g., gallstones lodged in thepancreatic or common duct). When acute pancreatitis becomes severe,treatment options are severely limited. Morbidity and mortality ratesfor pancreatitis are sobering. Baron, et al., “Acute NecrotizingPancreatitis”, New England J. of Medicine, Vol. 340, No. 18, pp.1412-1417 (1999) and Steer et al., “Chronic Pancreatitis”, New EnglandJ. of Medicine, pp. 1482-1490 (1995).

Down-regulating vagal activity can be used to treat pancreatitis. Arecently reported finding in experimental pancreatitis demonstrated thatthe vagus nerves are strongly implicated in the pathophysiology ofpancreatitis. Yoshinaga, et al., “Cholecystokinin Acts as an EssentialFactor in the Exacerbation of Pancreatic Bile Duct Ligation-Induced RatPancreatitis Model Under Non-Fasting Condition”, Japanese J. Pharmacol,Vol. 84, pp. 44-50 (2000). Pharmacologic means of decreasing pancreaticsecretion have been attempted with limited success because of thedose-limiting side effects encountered with the drugs, their lack ofspecificity or their lack of availability. In fact, one recent trial ofa specific blocker of parasympathetic (vagus nerves) control ofsecretion demonstrated a shortened recovery period in patients withacute pancreatitis while trials with other pancreatic down-regulatingdrugs that are less specific or potent have proven to be disappointing.Zapater, et al., “Do Muscarinic Receptors Play a Role in AcutePancreatitis?”, Clin. Drug Invest., 20(6), pp. 401-408 (2000); Norton,et al., “Optimizing Outcomes in Acute Pancreatitis”, Drugs, 61(11), pp.1581-1591 (2001). Atropine is a drug that blocks parasympathetic nerveendings. It is known to be desirable to use atropine in acutepancreatitis patients to down-regulate pancreatic activity.Unfortunately, for most such patients, this drug cannot be used due toits many side effects.

Acute pancreatitis patients may be placed on intravenous feeding withthe device 300 left in place for a chronic length of time (e.g., severaldays or weeks). At least the electrodes of the lower array 307 may beenergized with a blocking signal for the treatment of acutepancreatitis. The invention permits down-regulation of pancreatic outputthrough vagal blocking without the need for undesirable surgery fordirect vagal access.

In addition to utility for treating pancreatitis, the present inventionmay be used to avoid pancreatitis in patients having an increasedlikelihood of developing the disease. For example, patients undergoingendoscopic retrograde cholangiopancreatography (ERCP) and/or relatedprocedures are known to having a higher likelihood of developingpancreatitis. Such patients may be treated with the present inventionwith a blocking signal to down-regulate pancreatic output and reduce thelikelihood of developing pancreatitis.

Many physicians treating patients with pancreatitis use a nasogastrictube as part of the treatment. As a result, the present invention isillustrated as being incorporated on a nasogastric tube. However, asignificant body of physicians adheres to a belief that pancreatitispatients benefit from a feeding involving placing nourishment directlyinto the jejunum portion of the small intestine via a naso jejunal tube.While the present invention is illustrated in an embodiment of placementof the balloon and electrodes on a naso-gastric tube, the invention canalso be placed on a nasojejunal tube or a nasogastricjejunal tube.

Improvements to Control Nerve Down-Regulation

While simulating a vagotomy through a nerve block as described above isbeneficial, a complete and continuous block can have adverseconsequences in some patients. The vagus nerve serves a wide variety offunctions. For example, vagal activity contributes to pyloric relaxation(thereby promoting gastric emptying) as well as intestinal motility.Also, a vagotomized patient may experience a loss of the benefits of avagotomy over time. For example, over time, the enteric nervous systemmay compensate for a vagotomy. Therefore, in patients who haveexperienced weight loss from vagotomy, some patients may experience arelapse of weight gain over time as the enteric nervous systemcompensates for the loss of vagal activity. As a result, a complete andpermanent simulation of a vagotomy at times may be undesirable.

Animal studies performed by applicants reveal nerve and organ functionrecovery after cessation of a vagal blocking signal. In such studiespancreatic exocrine secretion is collected and measured in juvenilepigs. The collection of such secretions as a measure of vagal activityis described in Holst, et al., “Nervous control of pancreatic exocrinesecretion in pigs”, Acta Physiol. Scand. 105: 33-51 (1979) (in which anup-regulating stimulation of the vagus was studied).

Electrodes applied to both anterior and posterior vagal trunks areenergized with a blocking signal. The signal is applied for a limitedtime (e.g., 5 minutes). In response to vagal blocking, pancreaticexocrine secretion drops significantly (e.g., by up to about 90% frombaseline). After cessation of blocking, the level of pancreatic exocrinesecretion gradually increases toward baseline. The speed of vagalactivity recovery varies from subject to subject. However, 20 minutes isa reasonable example of the time needed to recover to baseline. Afterrecovery, application of a blocking signal again down-regulates vagalactivity which can then recover after cessation of the signal. Renewedapplication of the signal can be applied before full recovery. Forexample, after a limited time period (e.g., 10 minutes) blocking can berenewed resulting in average vagal activity not exceeding a levelsignificantly reduced when compared to baseline.

Recognition of recovery of vagal activity (and recognition of thesignificant variability between subjects) permits a treatment therapyand apparatus with enhanced control and enhanced treatment options. FIG.14 illustrates vagal activity over time in response to application of ablocking signal as described above and further illustrates recovery ofvagal activity following cessation of the blocking signal. It will beappreciated that the graph of FIG. 14 is illustrative only. It isexpected there will be significant patient-to-patient variability. Forexample, some patients' responses to a blocking signal may not be asdramatic as illustrated. Others may experience recovery slopes steeperor shallower than illustrated. Also, vagal activity in some subjects mayremain flat at a reduced level before increasing toward baselineactivity. However, based on the afore-mentioned animal experiments, FIG.14 is believed to be a fair presentation of a physiologic response toblocking.

In FIG. 14, vagal activity is illustrated as a percent of baseline(i.e., vagal activity without the treatment of the present invention).Vagal activity can be measured in any number of ways. For example,quantities of pancreatic exocrine secretion produced per unit time is anindirect measurement of such activity. Also, activity can be measureddirectly by monitoring electrodes on or near the vagus. Such activitycan also be ascertained qualitatively (e.g., by a patient's sensation ofbloated feelings or normalcy of gastrointestinal motility).

In FIG. 14, the vertical axis is a hypothetical patient's vagal activityas a percent of the patient's baseline activity (which varies frompatient to patient). The horizontal axis represents the passage of timeand presents illustrative intervals when the patient is either receivinga blocking signal as described or the blocking signal is turned off(labeled “No Blocking”).

As shown in FIG. 14, during a short period of receiving the blockingsignal, the vagal activity drops dramatically (in the example shown, toabout 10% of baseline activity). After cessation of the blocking signal,the vagal activity begins to rise toward baseline (the slope of the risewill vary from patient to patient). The vagal activity can be permittedto return to baseline or, as illustrated in FIG. 14, the blocking signalcan be re-instituted when the vagal activity is still reduced. In FIG.14, the blocking signal begins when the vagal activity increases toabout 50% of baseline. As a consequence, the average vagal activity isreduced to about 30% of the baseline activity. It will be appreciatedthat by varying the blocking time duration and the “no blocking” timeduration, the average vagal activity can be greatly varied.

The flexibility to vary average vagal activity gives an attendingphysician great latitude in treating a patient. For example, in treatingobesity, the blocking signal can be applied with a short “no blocking”time to reduce weight as rapidly as possible. If the patient experiencesdiscomfort due to dysmotility, the duration of the “no blocking” periodcan be increased to improve patient comfort. Also, the reduction ofenzyme production can result in decreased fat absorption withconsequential increase of fat in feces. The blocking and no blockingduration can be adjusted to achieve tolerable stool (e.g., avoidingexcessive fatty diarrhea).

The control afforded by the present invention can be used to prevent theenteric nervous system's assumption of control since vagal activity isnot completely interrupted as in the case of a surgical and permanentvagotomy. Further, pancreatic production of digestive enzymes (such asthe fat digesting enzyme lipase) is not eliminated but is controllablyreduced.

While patient weight loss and comfort may be adequate as feedback fordetermining the proper parameters for duration of blocking and noblocking, more objective tests can be developed. For example, theduration of blocking and no blocking can be adjusted to achieve desiredlevels of enzyme production and nutrient digestion. In one example ofdrug therapy for obesity, orlistat blocks the action of lipase. Lipaseis a fat-digesting enzyme. As a consequence of this reduction in lipase,the fat content of feces increases. It is generally regarded asdesirable to modulate drug intake so that fecal fat does not exceed 30%of ingested fat. Similarly, the blocking and no blocking durations canbe modulated to achieve the same result. Such testing can be measuredand applied on a per patient basis or performed on a statisticalsampling of patients and applied to the general population of patients.

FIG. 13 illustrates an embodiment with even more objective means tomodulating the block and no block durations. In FIG. 13, a sensingelectrode SE is added to monitor vagal activity. While sensing electrodeSE is shown as an additional electrode to blocking electrode BE, it willbe appreciated a single electrode could perform both functions. Thesensing and blocking electrodes are connected to a controller 102′.Controller 102′ is the same as controller 102 previously described withthe additive function of receiving a signal from sensing electrode SE(which yields the actual vagal activity of the graph of FIG. 14). Whenthe sensing electrode SE yields a signal representing a targeted maximumvagal activity or tone (e.g., 50% of baseline as shown in FIG. 14) thecontroller 102′ energizes the blocking electrode BE with a blockingsignal. As described with reference to controller 102, controller 102′can be remotely programmed as to parameters of blocking duration and noblocking duration as well as targets for initiating a blocking signal

As shown above, the present invention uniquely uses a recovery of thevagus nerve to control a degree of down-regulation of vagal activity.This gives a physician enhanced abilities to control a patient's therapyfor maximum therapeutic effectiveness with minimum patient discomfort.

With the foregoing detailed description of the present invention, it hasbeen shown how the objects of the invention have been attained in apreferred manner. Modifications and equivalents of disclosed conceptssuch as those which might readily occur to one skilled in the art, areintended to be included in the scope of the claims which are appendedhereto.

We claim:
 1. A method for treating obesity comprising: positioning afirst electrode on a vagus nerve of an obese patient at a location belowa vagal innervation of the heart, with the vagus nerve innervating atleast one alimentary tract organ; treating the patient's obesity byapplying an electrical treatment signal to the electrode with theelectrical treatment signal having: a) a frequency selected for saidsignal to at least partially downregulate nerve impulses on said vagalnerve, wherein said signal has a frequency in excess of 200 Hz, andwithout simultaneously applying a neural impulse-inducing secondaryelectrical signal to the vagus nerve on a proximal side of said locationwhenever the electrical treatment signal is applied; and b) a pluralityof on-times separated by a plurality of off-times, said signal appliedduring said on-times and not applied during said off-times, wherein aduration of the off-times is selected in response to a signal from asensing electrode representing at least 50% of an activity of said vagalnerve as compared to baseline.
 2. A method according to claim 1, whereinapplication of said electrical signal is variable by a controller toalter a characteristic of said electrical treatment signal.
 3. A methodaccording to claim 2, wherein said electrical treatment signal isregulated to heighten a sensation of satiety of said patient.
 4. Amethod according to claim 1, wherein the duration of said off times arealso selected to increase weight loss.
 5. A method according to claim 1,wherein said frequency is selected to block afferent signals on thevagus nerve.
 6. A method according to claim 1, wherein said frequency isselected to block efferent signals on the vagus nerve.
 7. A methodaccording to claim 1, wherein said frequency is selected to block bothafferent and efferent signals on the vagus nerve.
 8. A method accordingto claim 1, wherein said frequency is at least 500 Hz.
 9. A methodaccording to claim 1, wherein said sensing electrode is located in thefirst electrode.
 10. A method according to claim 1, wherein said sensingelectrode is located distal to the first electrode.
 11. A methodaccording to claim 1, wherein the electrical treatment signal is appliedto a vagal trunk.
 12. A method according to claim 1, wherein theelectrical treatment signal is applied to both an anterior vagus nerveand a posterior vagus nerve of the patient.
 13. A method according toclaim 1, further comprising monitoring a vagal activity of said patient.14. A method according to claim 13, wherein said monitoring includeselectrically monitoring a neural activity of said patient using thesensing electrode.
 15. A method according to claim 1, wherein said offtimes are varied to obtain an average vagal activity of at least 30%.16. A method according to claim 1, wherein said on times are about twoto five minutes.